Antigen epitope-TLR7/8a conjugate as self-assembled carrier-free nanovaccine for personalized immunotherapy

Epitope-based vaccine is a promising personalized cancer immunotherapy; however, a simple and ef-fective approach for its bulk manufacturing is challenging. Current vaccination strategies complicate the process by introducing unnecessary components such as additional delivery carriers, and assembly units. Herein, a type of toll-like receptor 7/8 agonist-epitope conjugate (termed as TLR7/8a-epitope) has been developed as a self-assembled and carrier-free nano vaccine platform, which effectively introduces the antigen and adjuvant with maximum precision, resulting in significantly enhanced dendritic cells (DCs) activation through the MyD88-dependent TLR signaling pathway. TLR7/8a-epitope nanovaccine can pro-long the local retention and increase drainage efficiency into the lymph node, eliciting a significantly higher level of CD8 T-cell immunity than those of conventional vaccine formulations. The immuniza-tion with TLR7/8a-epitope nanovaccine in mice can not only resist the invasion of B16 cancer cells, but also produce significant therapeutic effects against established B16 melanoma tumors. Therefore, the TLR7/8a-epitope nanovaccine, developed by the direct chemical conjugation of antigen peptide with im-munoadjuvant, has great advantages of clear and leanest compositions, controllable and definite prepa-ration process, and remarkable therapeutic effects, representing a new appraoch for personalized cancer immunotherapy. Statement of significance Herein, a kind of toll-like receptor 7/8 agonist-epitope conjugate was developed and spontaneously self-assemble into nanostructure in aqueous solution without the use of any additional constituents, which can be termed as unique carrier-free nanovaccine platform, providing effectually the leanest vaccine com-ponents with maximally and precisely loading of antigen and adjuvant. Significantly, the nanovaccine augmented the immunogenicity of antigenic peptide by increasing DCs activation through MyD88-mediated TLR signaling pathways and promoting T-cell priming. Moreover, nanovaccines could prolong the local retention and further increase the efficiency of drainage into dLNs, which was contributing to efficient initiation of epitope-specific memory and effector T-cell immune re-sponses, leading to effective prophylactic and therapeutic antitumor effects. (C) 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Automated summary

An epitope-based vaccine platform has been developed, which self-assembles into nanostructures without the use of additional carriers. It effectively introduces antigen and adjuvant, enhances dendritic cell activation and T-cell immunity, and shows potential therapeutic effects.